Background: The risk of sexually transmitted infections (STI) arises when there is unsafe sexual activity. Unsafe sex often begins in the teenage years, and it will persist as long as there is the opportunity for risky sexual activity. The purpose of this study was to assess the sexual risk behaviors and related factors of sexually-active adolescents in educational institutions. Methods: This was cross-sectional survey using an Internet-based application in schools in Bangkok from November 2020 to February 2021 with a total of 6,167 high school and vocational students. In the study, 14.1% of all participants had had sexual intercourse before the survey. By gender, 42.1% of the sexually-active students were males, and 57.9% were females. Indicators of risky sex include: (1) Not using a condom, (2) Having more than one sex partner; (3) Having sex in exchange for cash or in-kind compensation; and (4) Having sex without consent.Results: Of a total of 872 sexually-active participants, 590 (67.7%) had sex risk behavior. The multivariate logistic regression analysis identified the following statistically-significant factors related to risky sex: Alcohol use (AOR = 1.29; 95% CI: 1.03–2.78); vaping (AOR = 1.59; 95% CI: 1.01–2.53); cannabis use (AOR = 3.71; 95% CI: 1.51–9.09); gambling (AOR = 1.73; 95% CI: 1.23–2.44); unintended pregnancy (AOR = 2.80; 95% CI: 1.21–3.57); non-use of contraception (AOR = 3.25; 95% CI: 2.26–4.68); history of childhood sex abuse (AOR = 1.67; 95% CI: 1.05–2.68).Conclusions: Our findings suggest that, in designing and implementing sexual risk prevention programs for adolescents in educational settings, there is a need to highlight the role of substance abuse in relation to sexual risk behaviors. Programs should target both male and female students. Teenagers who use marijuana are more likely to be sexually active than those who have never used marijuana. These potential risks should be taken into account with respect to legalization of marijuana and recreational use of this drug.